These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: DNA interstrand cross-link and free radical formation in a human multidrug-resistant cell line from mitomycin C and its analogues.
    Author: Dusre L, Rajagopalan S, Eliot HM, Covey JM, Sinha BK.
    Journal: Cancer Res; 1990 Feb 01; 50(3):648-52. PubMed ID: 2153443.
    Abstract:
    A subline of the human breast tumor cell line (MCF-7), selected for resistance to Adriamycin and having the multidrug resistance phenotype, also developed significant cross-resistance to mitomycin C and its two analogues, BMY 25282 and BMY 25067. Because mitomycin C and the analogues contain both quinone and aziridine moieties, the mechanism of tumor cell kill is thought to involve alkylation and cross-linking of DNA molecules, hence they are not expected to show cross-resistance to cells selected for resistance to a DNA intercalator. Studies to understand this novel observation show that the resistant MCF-7 cells form significantly less hydroxyl radical and DNA cross-linking in the presence of mitomycin C and BMY 25282 than the sensitive cells. Although BMY 25067 formed less free radicals in the resistant cells, similar to the other two drugs, the formation of DNA cross-links was identical in both cell lines, indicating a somewhat different mechanism of tumor cell kill by this analogue. DNA cross-link formation increased slightly with time in the sensitive cells while there was a small decrease in the resistant cells. This difference in the formation of toxic intermediates appeared to result from enhanced detoxification of reactive species (hydrogen peroxide and alkylating intermediates) as a result of significantly higher glutathione peroxidase (14-fold) and glutathione S-transferase (44-fold) activities in the resistant cell line. These events, i.e., free radical formation and DNA alkylation, showed a good correlation with the cytotoxicity in drug-sensitive cells, indicating that both mechanisms contribute to cell killing of human breast tumor cells.
    [Abstract] [Full Text] [Related] [New Search]